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Immunoglobulin-G4-related disease (IgG4-RD) is an autoimmune-mediated spectrum of diseases, characterized by infiltration of IgG4+ plasma cells into one or multiple organs, with the pancreas being the most commonly affected organ. The disease mostly affects middle-aged to elderly men. Diagnosis requires an integration of clinical, radiologic, pathologic, and serologic studies. Histologically, there is an increased infiltration of IgG4+ plasma cells, elevated ratio of IgG4+/IgG plasma cells of more than 40%, and a storiform pattern of fibrosis. There may be eosinophilia, along with elevated IgG4 levels. IgG4-RD can mimic several diseases and should be differentiated from inflammatory and neoplastic processes. Recently, there has been increased awareness of cutaneous involvement by IgG4-RD either as an isolated lesion or primary involvement or as a secondary involvement from a systemic disease. Clinically, cutaneous IgG4+-related disease presents as papules, plaques, and nodules involving the head and neck areas. We have provided a systematic review of the literature of this new and challenging entity of cutaneous IgG4-RD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in melanocytic lesions. A series of 10 cutaneous melanomas and 24 benign melanocytic lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle upon Tyne, UK) was scored by an average of the mean labeling intensity; no nuclear staining = 0, weak nuclear staining = 1, moderate = 2, and intense = 3. Ets-1 expression was statistically assessed by the one-way analysis of variance (ANOVA) comparing the mean labeling intensity of melanoma to benign melanocytic nevi. All of the benign melanocytic lesions exhibited negative to weak nuclear staining, with an average mean labeling intensity of 0.4. Melanoma in situ exhibited moderate nuclear staining, for a mean labeling intensity of 2.0, whereas all conventional invasive melanomas exhibited moderate to strong nuclear staining, with a mean labeling intensity of 2.7. Metastatic melanoma exhibited very strong nuclear staining, with a mean labeling intensity of 3.0. Invasive desmoplastic melanoma, like melanoma in situ, showed moderate nuclear staining with a mean labeling intensity of 2.1. There was a trend toward more intense staining with melanoma progression. A statistically significant difference in the mean labeling intensity of Ets-1 was seen between invasive melanoma and benign melanocytic nevi (P <.0001). Ets-1 oncoprotein expression, however, does not distinguish among benign melanocytic lesions. Staining intensity and pattern might be a useful adjunct with histomorphology in distinguishing invasive melanoma from benign melanocytic nevi. Furthermore, Ets-1 expression may be an important pathogenic mechanism and predictor of aggressive biologic behavior of cutaneous melanoma, with a trend toward staining intensity increasing as Clark stage increases.

Background: Telepathology involves the use of video technology to facilitate remote-site diagnosis. To our knowledge, no studies have compared the reproducibility of real-time telepathology between dermatopathologists with that of traditional 2-headed microscopy in the diagnoses of routine dermatopathologic entities., Observations: The kappa statistic for both techniques was favorable: 0.76 (telepathology) vs 0.93 (conventional 2-headed microscopy); P =.04. The time taken per case was 42 seconds (telepathology) vs19 seconds (conventional 2 -headed microscopy); P =.003., Conclusions: Telepathology between 2 remote diagnostic centers offers a feasible means of facilitating the remote-site diagnosis of routine dermatopathologic entities. Although diagnostic accuracy and time taken per case were acceptable with video-assisted diagnosis, conventional microscopy had significantly higher accuracy and shorter time per diagnosis.

Background: Multiple myeloma (MM) is a plasma cell dyscrasia characterized by a clonal proliferation of plasma cells that produces a monoclonal protein. There are dermatologic disorders that have been associated with MM, such as amyloidosis, cryoglobulinemia, POEMS syndrome, normolipemic plane xanthoma, and plasmacytoma. The high volume of patients with MM seen at our institution presents an opportunity to define more extensively the spectrum of cutaneous diseases seen in concert with MM., Design: We reviewed 2357 pathology reports of all patients with a diagnosis of MM to find those who had undergone a skin biopsy. Files were searched for bone-marrow diagnosis, and for type and number of transplants., Results: In all, 284 patients yielded 472 skin biopsy specimens (average 1.7/patient). Skin biopsy specimen diagnoses included neoplastic lesions, (111; 73 malignant, 38 benign), graft-versus-host disease (120), drug-related lesions (46), cutaneous eruption of lymphocyte recovery (3), thrombocytopenia-related lesions (9), normolipemic plane xanthoma (1), amyloidosis (1), Sweet's syndrome (7), panniculitis (1), papulosquamous lesions (18), bullous diseases (17), vasculitis (11), infectious lesions (41), granulomatous dermatitis (6), alopecia cicatrisata (1), nonspecific lesions (77), and unrelated lesions (2)., Conclusions: Skin biopsy specimens from patients with MM less than 60 days from transplant most commonly show sequelae of the transplant such as graft-versus-host disease, Grover's disease (as a result of leukocytopenia and fever, waiting for engraftment), drug eruptions, chemotherapy effect, thrombocytopenic effect, cutaneous eruption of lymphocyte recovery, and Sweet's syndrome (possibly as a result of granulocyte-macrophage colony-stimulating factor). Biopsy specimens taken more than 60 days from transplant most commonly show graft-versus-host disease, drug eruptions, and Sweet's syndrome but also show unrelated conditions such as neoplastic lesions, nevi, papulosquamous lesions, vasculitis, infections, and nonspecific changes.

Background: Syringocystadenoma papilliferum (SCAP) and verrucous cyst are two uncommon benign tumors. The simultaneous occurrence of the two lesions has not been reported before., Methods: We report four cases of the simultaneous occurrence of the two rare lesions as so-called collision lesions with a review of the literature., Conclusion: The relationship of SCAP with viral infection needs further investigation.

Introduction: Histologic vasculitis must be interpreted with caution, as there is considerable overlap in its clinical, histologic and immunologic presentations. Case report: A 42 year old woman presented with an plaque on the buttock that was tender to palpation, and had been present for six weeks. Physical examination revealed a large, erythematous plaque with focal areas of atrophy, pigmentation, small crusts, and small blisters. Skin biopsies for routine histology, direct immunofluorescence and immunohistochemical examination were taken. Methods: Skin biopsies for hematoxylin and eosin (H&E) examination, as well as for direct immunofluorescence, indirect immunofluorescence and immunohistochemistry studies were performed. Results: Examination of the tissue sections demonstrated an inflammatory process involving capillaries and small blood vessels within the dermis and panniculitic adipose tissue. Focal extravasation of red blood cells into the dermal interstitial tissue was also observed. A mild, focal, lobular panniculitis was also present. Direct immunofluorescence and immunohistochemistry demonstrated deposits of several antibodies on vessels throughout the dermis. In addition, anti-neutrophilic cytoplasmic antibodies and neutrophil extracellular traps were identified. Conclusions: Few vasculitic processes have pathognomonic histologic findings. Often, the dermatopathologist and clinician must work together, combining clinical, histologic and other laboratory data to determine the nature of the primary disease process. In our case, a diagnosis of vasculitis with autoimmune overlapping auoimmune syndromes represented the consensus diagnostic conclusion. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is globally epidemic. Several mucocutaneous diseases are well established in association with HCV infection. Few case reports describe the recently recognized HCV-related skin disorder termed necrolytic acral erythema (NAE). Methods: Thirty patients with NAE were identified in a university-based dermatology clinic in Cairo, Egypt. These patients were observed over time to document the clinical and histologic findings of this disorder. Results: All patients were infected with HCV. Erythematous papules arose most commonly on the dorsal aspect of the feet, particularly the dorsal surface of the great toe. Progression resulted in confluence into erythematous dusky plaques with adherent scale and central erosion. The eruption extended to involve the lower leg and other regions in some patients but never affected palms or soles, the nail bed, nail plate, or mucous membranes. Skin biopsy specimens from fully evolved lesions displayed psoriasiform changes in association with more characteristic findings of keratinocyte necrosis and papillomatosis. Limitations: We did not perform a prospective review of patients known to be infected with HCV. Patients were identified from a general clinic population and then assayed for HCV serology. Conclusions: NAE is a distinctive skin disorder associated with HCV infection in all cases reported to date. Recognition of this disease should alert practitioners to the need for viral testing and appropriate counseling of patients. [Copyright &y& Elsevier]

Background: Sezary syndrome (SS) is an erythrodermic cutaneous T-cell lymphoma with a leukemic component. Biopsies from these patients may suggest erythrodermic mycosis fungoides or SS but most often are not diagnostic. Additional methods are therefore usually needed to diagnose SS. These include a peripheral blood morphological assessment, flow cytometry, and gene rearrangement studies. The Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer has proposed criteria for the diagnosis of SS based on peripheral blood analysis. These include an increased T-cell count with a CD4/CD8 ratio of ≥10, in conjunction with evidence of a T-cell clone in the blood (Willemze et al., Blood 1997; 90: 354–371). Methods: We have conducted a study designed to obtain CD4/CD8 ratios by immunoperoxidase staining of skin biopsies, as opposed to flow cytometry. Fourteen biopsies from eight patients with SS and 14 control biopsies were evaluated for CD4/CD8 ratio via double immunostaining. Results: A CD4/CD8 ratio of >10 : 1 was seen in 85% of SS biopsies and 43% of controls with horseradish peroxidase used as the CD4 antibody. With alkaline phosphotase used as the CD4 antibody, 54% of SS biopsies and 21% of control biopsies exhibited a >10 : 1 ratio. We demonstrate that double-labeling immunoperoxidase staining with antibodies to CD4 and CD8 on skin biopsies is not specific for SS. By comparing the CD4/CD8 ratios from skin biopsies in Sezary cases with those from biopsies in inflammatory dermatoses cases, we conclude that flow cytometry remains the most specific method for determining the CD4/CD8 ratios in patients with cutaneous eruptions. Although immunohistochemistry would be useful for laboratories with limited access to flow cytometry, we dismiss such a use, as CD4/CD8 ratios ≥10 were also found in 21–43% of non-Sezary cases examined. Conclusions: We conclude that a CD4/CD8 ratio >10 : 1 on skin biopsy is not... [ABSTRACT FROM AUTHOR]

Cutaneous eruptions are frequent complications in the clinical course of patients with leukemia. Leukemia cutis is occasionally the cause of the eruption in many cases the lesions are non-leukemic. We have retrospectively selected all skin biopsies from patients with a computer-coded diagnosis of leukemia seen in the Stanford University Department of Pathologhy in the last 7 years, and separated these cases into the broad categories of acute myelogenous lejkemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL). We also analyzed separately those cases seen in patients treated with bone marrow transplantation from those treated with standard chemotherapy regimens. We found that leukemia cutis was seen frequently as the cause of lesions in patients with CML and CLL. In contrast, a wide variety of lesions were seen in patients with AML, including a greater number of infections lesions, drug reactions, vasculitis, and lesions secondary to a hemorrhagic diathesis. In the bone marrow transplantation patients, graft vs host disease was usually the cause of skin lesions in those transplanted for CML and ALL, but again those patients with an underlying diagnosis of AML showed a wide variety of lesions including drug reactions, fungal infections and leukemia cutis. Finally, 6% of cases from patients with AML showed intraepidermal blistering disorders of various types, an association that has been previously reported. [ABSTRACT FROM AUTHOR]

A 72-year-old Caucasian man presented with tender, hyperkeratotic, violaceous, ill-defined, scattered plaques associated with minimal pitting edema of the right upper extremity. He had been discharged 3 days earlier from an outlying community hospital after a 33-day admission for exacerbation of chronic obstructive lung disease requiring large doses of systemic corticosteroids. A right subclavian central venous line for intravenous access was placed after he developed a gastrointestinal bleed and myocardial infarction. The clinical differential diagnosis of the eruption on the right upper extremity at the time he presented to our service included cellulitis, deep venous thrombosis, and brachial plexus neuropathy. Brachial plexus neuropathy was ruled out with normal electromyography, nerve conduction studies, and cervical spine radiographs. Deep venous thrombosis was never completely eliminated, because the patient refused a venogram and the venous Doppler exam was nondiagnostic. Treatment for a presumed bacterial cellulitis was initiated with Nafcillin intravenously. As there was clinical disease progression without appreciable improvement by day nine (Fig. 1 and 2), a skin biopsy was performed and topical Nystatin powder was added for possible yeast etiology. Bacterial cultures were negative; however, fungal cultures on Sabouraud’s agar were positive for Paecilomyces lilacunis after 15 days. Histologic sections demonstrated skin with an essentially normal epidermis. Within the dermis, there was an extensive, mixed, granulomatous inflammatory infiltrate with abundant multinucleated giant cells. Necrosis was not abundant. Occasional 8–12 μm yeast-like organisms were apparent within the cytoplasm of multinucleated cells and in an extracellular location, together with occasional hyphal forms with irregular branching. Periodic acid–Schiff (PAS) with diastase and Gomori methenamine silver accentuated the staining and confirmed the fungal... [ABSTRACT FROM AUTHOR]

T lymphocytes bearing the γ/δ T-cell receptor are a rare component of normal human GI epithelium and skin. Recently, however, an unusually high percentage of T lymphocytes with γ/δ receptors has been described in gastrointestinal biopsies from patients with dermatitis herpetiformis, implicating the γ/δ T cell subset in the pathogenesis of this disease. We investigated a possible role for this subset of lymphocytes in the pathogenesis of the cutaneous lesions of dermatitis herpetiformis. Using a standard immunoperoxidase technique, we labelled perilesional skin biopsies from patients with dermatitis herpetiformis and other inflammatory dermatoses with monoclonal antibodies to CD3, CD4, CD8, α/β T cell receptor. %gamma;/δ T cell receptor, and IL-2 receptor. We found no differences in the percentage of γ/δ positive. T lymphocytes in skin lesions of dermatitis herpetiformis as compared to other selected inflammatory conditions. These findings suggest that the pathogenesis of the cutaneous lesions of dermatitis herpetiformis is not mediated through γ?δ T cells, and that the cutaneous lesions may develop through mechanisms different from those operative in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune bullous skin diseases (ABDs) represent a heterogeneous group of disorders of the skin and mucosa; these disorders are commonly associated with deposits of immunoglobulins, complement, and fibrinogen, usually directed against distinct adhesion molecules. Methods: We utilized hematoxylin and eosin (H & E) stained tissues sections to evaluate for the presence of rouleaux in lesional skin biopsies of patients affected by ABDs including patients with endemic and nonendemic pemphigus foliaceus, bullous pemphigoid (BP), pemphigus vulgaris (PV), dermatitis herpetiformis (DH), and a group of controls taken from routine biopsies seen in our practice. Results: Most autoimmune bullous skin diseases biopsies showed rouleaux formation within and around post-capillary venules in the superficial vascular plexus in association with a pinkish brush-like material that resembles fibrin or other amorphous eosinophilic material. Discussion: We document that rouleaux and the pinkish aggregates are present in within biopsies taken from lesional skin in the majority of patients with ABDs and speculate that this maybe as result of the exocytosis of inflammatory cells, antibodies that form when exposed to the extracellular matrix which is already edematous in most ABDs. In addition red blood cells in the presence of plasma proteins or other macromolecules may form aggregates. Further studies are needed. [ABSTRACT FROM AUTHOR]

Scedosporium apiospermum, the asexual stage of Pseudoallescheria boydii, is a fungus ubiquitous in soil as well as organically polluted areas, where nitrogen-containing compounds are abundant. It is an emerging opportunistic pathogen that can range from cutaneous to disseminated infection and can be fatal within months of diagnosis. Here we present a case of disseminated S. apiospermum infection with cutaneous manifestations in a 59-year-old woman with myelodysplastic syndrome, in remission from chronic lymphocytic leukemia, presented with pneumonia and deteriorating mental status. An X-ray computed tomography scan showed three non-contrast-enhancing hypodensities affecting the brain. Many erythematous, indurated skin lesions, measuring 3-5 mm in diameter, were noted on her chest, shoulders and arms. Biopsies were submitted for culture and histology. Histopathologic examination revealed superficial and deep perivascular and periadnexal inflammatory infiltrates of lymphocytes and neutrophils. Scattered collections of fungal organisms were noted near the eccrine glands. The periodic acid Schiff with diastase stain showed the presence of variable sized spores and hyphae with some acute angle branching. Both tissue and blood cultures were positive for a single Scedosporium species. Histologically, eccrine or peri-eccrine involvement by fungi may be an important finding for Scedosporium infection of the skin. Harrison MK, Hiatt KH, Smoller BR, Cheung WL. A case of cutaneous Scedosporium infection in an immunocompromised patient. [ABSTRACT FROM AUTHOR]

Context: Bullous allergic reactions are inflammatory skin disorders, presenting usually as a result of some type of reaction to medication. Case Report: A 67-year-old female was evaluated for the presence of diffuse patches of erythema, microvesiculation, vesicles, crusts, and oozing of sudden appearance on the extremities and on the rest of the body after taking sulfamethoxazole in combination with trimethoprim. Skin biopsies for hematoxylin and eosin examination, as well as for direct immunofluorescence and immunohistochemistry analysis were performed. H&E staining demonstrated classic features. Direct immunofluorescence revealed strong deposits of fibrinogen in the vessels of the skin. The immunohistochemistry stain showed strong positivity of myeloperoxidase within the blister cavity. The distribution of the vessels around the inflammatory process were noticed by using antibodies to CD34 as well to collagen IV. Conclusions: sulfamethoxazole is catalysed by CYP2C9 and/or myeloperoxidase. Thus, myeloperoxidase appears to be of importance in this disorder. [ABSTRACT FROM AUTHOR]

BACKGROUND. A benign cutaneous mesenchymal lesion with features of dermatofibroma, dermatomyofibroma, and lipoma is described. OBJECTIVE.An attempt is made to classify this previously undescribed entity. METHODS. Tissue sections were studied with routine hematoxylin and eosin and a battery of immunoreactants to ascertain the nature of the cells within the lesion. RESULTS. The lesion described has a unique histologic appearance, containing elements of mature adipose tissue, smooth muscle, and fibrous tissue. CONCLUSION. Our findings suggest that this tumor is a distinct entity that is not exactly like any previously described lesion and we have given it a descriptive name. [ABSTRACT FROM AUTHOR]

The article discusses the detection of clonality with immunohistochemical analysis in cutaneous plasmacytomas. The article seeks to demonstrate clonality using κ and λ immunohistochemical analysis in cutaneous plasmacytomas and to ascertain whether or not interpretation is hindered by background staining. Cutaneous plasmacytoma is an infrequent manifestation in patients with multiple myeloma (MM), occurring in 0.59% of patients. In MM, cutaneous plasmacytoma may occur in 3 clinical settings, including the initial manifestation of MM, direct extension from a bony lesion, and part of multiple site involvement.